Delirium in Pediatric Critical Care-2017

Delirium in Pediatric
C r i t i c a l C a re
a b,c,d e,
Anita K. Patel, MD , Michael J. Bell, MD , Chani Traube, MD *
KEYWORDS
Delirium Pediatric critical care Pediatrics Pain Agitation Sedation
KEY POINTS
Delirium is a frequent and serious complication of pediatric critical illness.
Pediatric delirium is associated with increased morbidity, including longer duration of me-
chanical ventilation, increased hospital length of stay, and higher resource utilization.
Benzodiazepines likely increase the risk for development of pediatric delirium.
Delirium in children is both treatable and preventable.
DELIRIUM IN PEDIATRIC CRITICAL ILLNESS

Introduction
As critical care medicine has matured over the decades, from a specialty fighting mor-
tality from a myriad of diseases to one promoting recovery with as few disabilities as
possible, mitigating complications of critical illness has become one of the intensivist’s
most important goals.1 The sudden onset of unexplained deterioration of conscious-
ness can be particularly worrisome. In critical illnesses such a deterioration of senso-
rium may represent delirium, which is characterized by an acute onset and fluctuating
course with disturbances in awareness and cognition.2 In adults, delirium occurs
frequently and represents global cerebral dysfunction due to the direct physiologic ef-
fects of an underlying medical illness or its treatment.2,3 Although delirium is generally
a temporary state, it is strongly associated with poor outcomes, including increased
mortality, and long-term cognitive impairment in survivors.4,5 Because of the extensive
research highlighting the morbidity associated with delirium, the Society of Critical
Care Medicine (SCCM) released guidelines in 2013 that recommended routine
Disclosure Statement: All authors declare they have no relevant financial interests to disclose.
a
Pediatrics, Children’s National Medical Center, 111 Michigan Avenue Northwest Suite M4800,
Washington, DC 20010, USA; b Critical Care Medicine, University of Pittsburgh, 3434 Fifth
Avenue, Pittsburgh, PA 15260, USA; c Neurological Surgery, University of Pittsburgh, 3434
Fifth Avenue, Pittsburgh, PA 15260, USA; d Pediatrics, University of Pittsburgh, 3434 Fifth
Avenue, Pittsburgh, PA 15260, USA; e Pediatrics, Weill Cornell Medical College, 525 East 68th
Street, M-508, New York, NY 10065, USA
* Corresponding author.
E-mail address: chr9008@med.cornell.edu
Pediatr Clin N Am 64 (2017) 1117–1132

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1118 Patel et al
monitoring for delirium in critically ill adults as standard of care.3 A recent body of pe-
diatric literature suggests that this recommendation should apply to children as well.6,7
Pathophysiology
The cause of delirium is complex, with many possible pathophysiologic pathways.
Most researchers think that delirium results from a combination of predisposing and
precipitating factors. Predisposing factors are patient related (for example, age, ge-
netic susceptibility, or underlying disease). Precipitating factors include treatment ef-
fects (particularly sedative medications) and the intensive care unit (ICU)
environment.3,8,9 Here the authors highlight 3 processes that are thought to play
important roles in the evolution of pediatric delirium.
The neuroinflammatory hypothesis suggests that systemic inflammation (commonly
seen during critical illnesses, such as respiratory failure, sepsis, and others) leads to
either compromise in the integrity of the blood-brain barrier or de novo production
of inflammatory products within the brain.10 Inflammation leads to endothelial activa-
tion, enhanced cytokine activity, and infiltration of leukocytes and cytokines into the
central nervous system (CNS), producing local ischemia and neuronal apoptosis.11
Several studies have demonstrated elevated levels of proinflammatory cytokines in
delirious patients (such as C-reactive protein, tumor necrosis factor-alpha, and
interleukin-6) compared with nondelirious patients, even after controlling for age
and cognitive impairment.12–14
The neurotransmitter hypothesis was generated from clinical observations that
delirium often followed the use of medications that change neurotransmitter func-
tion.10 Studies show that impaired cholinergic function, coupled with an excess of
dopaminergic transmission, leads to the development of delirium.15–17 Notably, anti-
cholinergic medications are tightly associated with development of delirium in the geri-
atric population, as the elderly have an age-related reduction in acetylcholine
synthesis.18,19 (Intriguingly, a similar phenomenon may exist in children less than
2 years of age, whereby functional MRIs have demonstrated sparse connectivity be-
tween control structures related to executive function. This sparse connectivity results
in dependence on the cholinergic system to modulate attention and orientation. Like
the elderly, these young children may be at particular risk of delirium with exposure to
anticholinergic medication.)20,21 In addition to dopamine and acetylcholine, dysregu-
lation of melatonin, glutamate, norepinephrine, serotonin, histamine, and gamma-
aminobutyric acid has also been suggested to contribute to delirium development.10
The oxidative stress hypothesis suggests that reduced oxygen delivery in critical
illness, coupled with increased cerebral metabolism, leads to the production of reac-
tive oxygen species that cause global CNS dysfunction.10 Hypoxia has clearly been
associated with delirium development.22–24 For instance, a study of patients undergo-
ing cardiac surgery found that intraoperative desaturation was an independent risk
factor for postoperative delirium.23 Demonstrating that overlapping sources of patho-
physiology contribute to delirium, hypoxia also results in an excess of dopamine due
to the failure of the oxygen-dependent conversion of dopamine to norepinephrine. The
enzyme responsible for dopamine degradation, catechol-o-methyl transferase, is
inhibited by toxic metabolites produced during oxidative stress.22 An excess of dopa-
mine has been evidenced in multiple studies to underlie the pathogenesis of hyperac-
tive delirium.10
Regardless of the exact pathophysiology that triggers an episode of delirium, the
end result is the same: altered neurotransmission that leads to a failure of integration
and processing of sensory information and motor response. This final common
pathway leads to the behaviors that we recognize as delirium.25
Delirium in Pediatric Critical Care 1119
Clinical Presentation
There are 3 major subtypes of delirium recognized by the Diagnostic and Statistical
Manual of Mental Disorders, Fifth Edition: hyperactive, hypoactive, and mixed-type
delirium, with each having specific characteristics. Hyperactive delirium is character-
ized by agitation, restlessness, hypervigilance, and combative behavior. In contrast,
hypoactive delirium is notable for lethargy, inattention, and decreased responsive-
ness. Mixed-type delirium exhibits aspects of both hyperactive and hypoactive
delirium.2,3 Importantly, hypoactive delirium can be easily misdiagnosed as overseda-
tion or clinical depression without appropriate screening and diagnostic tools for
assessment.26–28 Unfortunately, hypoactive delirium has been associated with poor-
est prognosis and greatest frequency, emphasizing the need for diligent screening
for delirium in patients with critical illnesses.29,30 In a longitudinal study of pediatric
delirium and its subtypes, involving 1547 children and more than 7500 patient days,
hypoactive and mixed-type delirium were most common (46% and 45%, respec-
tively), whereas the hyperactive subtype was only found in 8% of patients.7 This profile
of delirium is consistent with observations of adults with critical illnesses.
Delirium in children is often marked by changes in psychomotor activity, ranging from
delayed responsiveness to constant, agitated movements. Emotional lability is also
common, evidenced by inconsolableness or, alternatively, inappropriate calmness.
Some pediatric patients (particularly adolescents) experience auditory and visual hal-
lucinations. Disordered sleep is nearly always present in delirious children.8,9,31,32
Preliminary evidence suggests that delirium often occurs early in the ICU course of
children with critical illnesses, with a median time to development of delirium of 1 to
3 days in pediatric studies.7,33–35 Furthermore, the few studies that have been con-
ducted to assess the duration of delirium suggest it is a relatively brief condition,
with a median of 2 days.7,33,34 A substantial portion (approximately one-third) of pa-
tients with early onset delirium will demonstrate recurrent episodes during their ICU
stay.7,33
Regardless of its duration or timing, delirium has measurable effects on a variety of
outcomes. In a recent study of postoperative delirium in children, 2 patterns of delirium
were described. For approximately half of the children, delirium was diagnosed early in
the course of their illness (within 24 hours), was of short duration (less than 24 hours),
and was characterized by relatively low scores on the Cornell Assessment of Pediatric
Delirium (CAPD). Within this series, these children were categorized as having mild
delirium. In contrast, another cohort of children experienced delirium throughout the
study period (5 days) and were categorized as having severe delirium. Compared
with children who were never delirious, those with mild delirium had increased time
on mechanical ventilation and longer hospital length of stay (LOS), whereas those
with severe delirium had even longer hospitalizations, took longer to emerge from
sedation, had longer time to extubation, and had higher resource utilization.34
Epidemiology
Delirium in adults is a well-known problem, with many hospitals implementing delirium
scoring plans, because more than 30% of all critically ill adults develop delirium during
their ICU stay.3,36 Delirium research in pediatrics lagged behind because of the lack of
validated screening tools and a decreased awareness of this condition among
clinicians.
Recent reports have found that pediatric delirium is quite frequent, with prevalence
rates between 12% and 65% in pediatric medical, surgical, and cardiac ICUs.6 In one
of the earliest series in the field, a prevalence of 12.3% was reported; but this cohort
1120 Patel et al
included only children older than 5 years and only 6% of the children were mechani-
cally ventilated (MV).37 In another cohort of children (0–21 years of age, 25% on MV), a
delirium prevalence rate of 22% was observed. In this study, delirium was associated
with age less than 5 years and preexisting developmental delay.38 In a study of chil-
dren with heart disease cared for in a cardiac ICU, a delirium prevalence of 49%
was observed, largely comparable with adults with heart disease.33 In the surgical
population, a prevalence rate of 27% was described, with an overall delirium inci-
dence of 65% in children within 5 days after surgery. (In this study, many subjects
were infants after cardiac bypass procedures).34 Another cohort study that included
children within a limited age range (6 months to 5 years) found an overall prevalence
of 47%; the highest rate (56%) was found in children younger than 2 years of age.35 A
large-scale, longitudinal study of delirium in all patients admitted to a single pediatric
ICU (PICU) over a 1-year period of time, including more than 1500 patients, demon-
strated a delirium rate of 17%.7 It should be noted that this unit was an early adopter
of delirium screening and had systematically changed its approach to sedation and
management to minimize delirium risk. So it is likely that this 17% incidence is lower
than rates in other institutions that have not been leaders in delirium screening.7 In the
largest multi-institutional pediatric delirium study to date, 994 children were assessed
for delirium in 25 different PICUs. Delirium prevalence overall was 25%.39
Risk Factors
It is useful to separate risk factors for pediatric delirium into 2 categories: modifiable
and nonmodifiable (Table 1). Independent risk factors for delirium development in crit-
ically ill adults include high severity-of-illness score on admission, elderly age, hyper-
tension, dementia, alcoholism, and cigarette use. Hospital-related risk factors for
delirium development in adults include depth of sedation, receipt of benzodiazepines,
and use of restraints.3
Demographic risk factors for development of delirium in children include age less
than 5 years and preexisting diagnosis of neurodevelopmental delay. It is not surpris-
ing that both the immature and abnormal brains, respectively, are more prone to
development of delirium; this is similar to the finding of increased delirium in the
elderly, and in those with underlying dementia.7,25,33,35,39
Children with higher severity-of-illness scores on admission are more likely to
develop delirium. Delirium, in turn, then contributes to multiple organ dysfunction syn-
drome, as delirium itself is an indication of end-organ (brain) dysfunction.7,33,34,40
Duration of ICU stay likely contributes to delirium development, but this relationship
is difficult to understand as a prolonged LOS likely exposes children to increased
Table 1
Risk factors for development of delirium
Predisposing Risk Factors Precipitating Risk Factors

Age <2 y Anticholinergic medications
Developmental delay Benzodiazepines
High severity of illness Cardiac bypass surgery
Low albumin Immobilization
Mechanical ventilation Prolonged ICU length of stay
Preexisting medical condition Restraints
Risk factors for delirium can be separated into predisposing and precipitating risk factors. It is
important to recognize that several risk factors are modifiable.
factors associated with delirium – and delirium also causes increased LOS.7,25,33,34 To
attempt to understand this relationship, an international study showed an increase in
delirium rates after 5 days in the ICU (20% in children with LOS 5 days vs 38% in
children with LOS >5 days, P<.001).39
Risk factors particular to children with congenital heart disease have been identified
as well. Specifically, cardiac bypass surgery is thought to be a unique exposure,
marked by a significant inflammatory response to the cardiotomy and bypass circuit,
or possibly subclinical evidence of emboli during bypass.41,42 Incidence of pediatric
delirium after cardiotomy was strongly and independently associated with longer
bypass times and greater complexity of the surgical repair. Children with cyanotic le-
sions were at increased risk for delirium, supporting several theories of delirium devel-
opment, including those associated with hypoxia and oxidant stress. Poor nutritional
status (using a preoperative albumin level <3 mg/dL as a surrogate marker for ade-
quacy of nutrition) also strongly predicted delirium.33
Importantly, recent research has identified potentially modifiable risk factors for
delirium development. A prospective observational study (n 5 1540 children) used a
multivariable model to demonstrate a 5-fold risk of delirium in children who were
ever prescribed benzodiazepines (after controlling for severity of illness, develop-
mental delay, mechanical ventilation, and other important confounders).7 However,
an assessment of the relationship between benzodiazepine use and delirium can be
confounded by the fact that a child with hyperactive delirium could be prescribed ben-
zodiazepines as a treatment of agitation. Therefore, it is important to assess the clin-
ical context in much more detail. This was done in a longitudinal study that followed
every child in a PICU throughout hospitalization. Each child was prospectively
assigned a daily cognitive status of (1) delirium, (2) coma/deep sedation, or (3) delirium
free/coma free. In this circumstance, and only considering children who developed
next-day delirium (ie, a child who developed delirium after scoring delirium free/
coma free the previous day), benzodiazepines remained independently associated
with delirium (odds ratio [OR] 3.14, confidence interval 2.08–4.74, P<.001) after
controlling for multiple covariates. In addition, an analysis of benzodiazepine
doses administered to 539 critically ill children showed a dose-response effect,
with delirium rates of 79% in those who received greater than 0.82 mg/kg/d of mida-
zolam equivalents as compared with a 27% delirium rate in children given less than
0.82 mg/kg/d (P<.001).7
A multi-institutional point prevalence study demonstrated that odds of delirium
quadrupled in patients who were physically restrained. Although this analysis was
controlled for mechanical ventilation and use of sedating medications, temporality
was not assessed (and it is possible that children were restrained after developing
delirium).39 However, it is consistent with a large body of adult literature that shows
a clear relationship between use of physical restraints and subsequent development
of delirium.3,36,43,44
Outcomes
Delirium that develops in adults with critical illnesses has been associated with poor
outcomes, including a 3-fold increased risk of mortality, increased ICU and hospital
LOS, longer time on mechanical ventilation, long-term cognitive impairment, and
post–intensive care syndrome.3–5,45,46 Additionally, delirium has been linked to
increased rates of auto-extubation and inadvertent removal of catheters.3
Preliminary studies strongly suggest a similar pattern in children with critical ill-
nesses. Pediatric delirium has been linked to short-term morbidity, including increased
duration of mechanical ventilation in children with delirium (median 4 vs 1 day, P<.001).7
1122 Patel et al
Several studies have shown that delirium is associated with increased length of hospital
stay. In fact, in a cardiac ICU cohort, delirium was independently associated with an in-
crease in LOS of 60%.33 In a general PICU, adjusted relative LOS was 2.3 in children
with delirium, after controlling for mechanical ventilation and severity of illness on
admission.7 In yet another study, delirium predicted increased hospital LOS, increased
duration of mechanical ventilation, and higher resource utilization; the extent of in-
creases was directly related to duration of delirium.34
From a financial perspective, a diagnosis of delirium in children has been associated
with increased health care costs. In a single-center study, daily PICU costs were 23%
higher for an ICU day with delirium as compared with an ICU day without delirium. Inci-
dence of delirium was associated with an overall 85% increase in hospital costs (rela-
tive costs 1.85 [1.51–2.26], P<.001), even after controlling for severity of illness, PICU
LOS, and other important confounders. This increase translates into more than $500
million each year in US hospital costs alone.47
A prospective pediatric study has shown a strong and independent association be-
tween pediatric delirium and mortality, with an adjusted OR of 4.4 for in-hospital death
in children who were diagnosed with delirium. In this cohort delirium was a stronger
predictor of mortality than the Pediatric Index of Mortality 3 score (OR of 3.2 in patients
in the highest severity-of-illness category). Delirium may be an important identifier of
children who are most vulnerable to poor outcomes.7 To date, there are no long-
term studies published that describe the association between delirium and cognitive
outcomes in children after discharge or the effect of delirium on the long-term psycho-
logical and emotional health of PICU survivors and their families.
Diagnosis
Until the advent of bedside screening tools, pediatric intensivists relied on consultation
with pediatric psychiatrists to make the diagnosis of delirium. Not surprisingly, psychi-
atrists were usually only consulted in extreme cases, when delirium resulted in disrup-
tive and aggressive behaviors that interfered with the medical team’s management
plans or the symptoms were so extreme as to require an expansion of the differential
diagnosis to other possible neurologic conditions.30,48,49 A psychiatric assessment,
although reliable, is not available for point-of-care use in every child in the PICU.50
As in adults, there was a need to establish delirium screens for nonpsychiatrists to
use routinely at the patients’ bedside.
It would not be possible to simply adopt delirium tools designed for adults, as diag-
nosing delirium in children is complicated by developmental variability. The behavior
expected from a hospitalized 2-year-old child, as compared with a 16-year-old adoles-
cent, are vastly different; appropriate developmental expectations are necessary.51 As
pediatric clinicians became aware of the significant burden of delirium in adult ICUs, it
was clear that it was necessary to develop child-specific bedside screening tools.8,9,52
Two different versions of pediatric delirium screens were developed: the Pediatric
Confusion Assessment Method for the ICU (pCAM-ICU or psCAM-ICU for
preschool-age children) and the CAPD. Both have been proven to be valid and reliable
for detection of delirium in critically ill children. Each requires that the child be arous-
able to verbal stimulation in order to be assessed. Both the pCAM-ICU and CAPD
should take only minutes to complete.6,35,37,38,53
The pCAM-ICU/psCAM-ICU are interactive, cognitively oriented screens (Fig. 1).
The pCAM-ICU is designed for patients older than 5 years, and the psCAM-ICU is
designed for children aged 6 months to 5 years. These tools are point-in-time screens,
designed to detect delirium that is present at the time of testing. The interactive nature
of the tool should yield objective results (delirium present or absent).35,37
Fig. 1. pCAM-ICU. The pCAM-ICU is an interactive cognitively oriented tool validated in chil-
dren from 5 to 18 years of age. (Available at: http://www.icudelirium.org/docs/ped_
Instruction-Tool_pCAM-ICU_9-2016.pdf. Accessed July 10, 2017.)
The CAPD is an observational screen that provides a longitudinal picture of a pedi-

atric patient over the course of a nursing shift (usually 8–12 hours) (Table 2). It is suit-
able for use in children 0 to 21 years of age and was validated in both developmentally
delayed and developmentally typical children. A score of 9 or higher is consistent with
a delirium diagnosis; the CAPD score can be trended within an individual patient over
time, allowing for assessment of trajectory and response to interventions.38
With availability of rapid, valid, and reliable bedside tools for use in children of all
ages, delirium screening has become feasible for use as standard of care in PICUs.
In fact, 3 years after the publication of the SCCM’s guidelines for adults, the European
Society for Pediatric and Neonatal Intensive Care released consensus guidelines in
2016 calling for “use of CAPD as an instrument to assess pediatric delirium (grade
of recommendation 5 A)” once each shift in critically ill children6. Routine monitoring
will allow providers to detect and treat delirium earlier and potentially improve
outcomes.3,6
Differential diagnosis
In children with underlying developmental delay, there is a need to establish alteration
from cognitive baseline before diagnosing delirium. In addition to a positive delirium
screen, the clinician needs to confirm that there is an acute process (ie, not merely
static encephalopathy) with a fluctuating level of awareness over the course of the
day.50,51
The classification of sedation-related delirium is controversial.54 This type is a specific
form of delirium that rapidly resolves once sedation is lifted and was noted in a protocol
1124 Patel et al
Table 2
Cornell Assessment for Pediatric Delirium
Please answer these questions based on your interactions with the patient over the course of
your shift:
Never 4 Rarely 3 Sometimes 2 Often 1 Always 0 Score
1. Does the child make eye
contact with the
caregiver?
2. Are the child’s actions
purposeful?
3. Is the child aware of his
or her surroundings?
4. Does the child
communicate needs and
wants?
Never 0 Rarely 1 Sometimes 2 Often 3 Always 4
5. Is the child restless?
6. Is the child inconsolable?
7. Is the child underactive:
very little movement
while awake?
8. Does it take the child a
long time to respond to
interactions?
TOTAL
The CAPD is an observational longitudinal tool validated in children from birth to 21 years of age.
(Available at: http://www.icudelirium.org/docs/capd.pdf. Accessed July 10, 2017.)
whereby adults were kept sedated for most of the day, with scheduled sedation breaks
to allow for a period of wakefulness. In the subset of patients with delirium limited to
rapidly reversible sedation-related delirium, outcomes were similar to patients who
did not experience delirium,55 suggesting that this was merely residual sedation and
not delirium. This finding has not been replicated in a recent pediatric study using the
CAPD, wherein delirium could be clearly distinguished from sedation by analysis of in-
dividual test items, and even mild delirium of short duration was associated with poor
outcomes.34 In fact, in a multicenter pediatric study, daily sedation interruption was
associated with an overall increase in exposure to narcotics and benzodiazepines,
increased time on mechanical ventilation, and increased length of hospital stay.56 This
finding highlights the importance of judicious sedation management in children.57
Iatrogenic withdrawal syndrome (IWS) can result in both the physiologic signs of
abstinence and the behavioral symptoms of agitation, confusion, and motor activity
that are consistent with hyperactive delirium. It is critically important to recognize
and treat the physiologic signs of withdrawal (ie, dilated pupils, diarrhea) with judicious
narcotic replacement.58
Treatment
When a child is diagnosed with delirium, the key to effective treatment is identifying the
underlying cause. Clinically, delirium can be thought of as a product of the underlying
illness, iatrogenic effects of treatment, and the ICU environment9,25,31 (Fig. 2). With a
stepwise approach, one should investigate for an underlying medical problem that
Fig. 2. Delirium treatment algorithm. With a systematic approach to targeting underlying

triggers of delirium, most children will improve. If agitated behaviors persist, clinicians
can consider pharmacologic treatment. a Note: This treatment is an off-label use of these
drugs, as the Food and Drug Administration has not approved either dexmedetomidine
or the atypical antipsychotics for treatment of pediatric delirium.
may have triggered the delirium episode. Delirium can be an early warning sign of
an evolving infection or the result of hypoxia or acute metabolic derangements. A
careful neurologic examination to exclude a primary CNS disease should be
considered.31,59,60
After assessing for underlying illness, addressing iatrogenic causes of delirium is
necessary. Optimizing pain control is essential, especially in preverbal children. Sed-
atives should be minimized, with consideration given to replacement of benzodiaze-
pines with dexmedetomidine if possible, as several studies suggest that
dexmedetomidine prevents and/or treats delirium.61–65 (It is important to note that
this is an off-label use, as the Food and Drug Administration has not approved dexme-
detomidine for the treatment of pediatric delirium.) A careful review of the patients’
medication list is warranted with consideration of discontinuing medications that
might be associated with delirium, if possible (particularly sedatives, anticholinergics,
and steroids).3,9,25 Identification of IWS is necessary, with judicious narcotic replace-
ment until the physiologic signs of withdrawal abate.58 But after treating IWS, the
agitated behavior of hyperactive delirium may persist and often requires environ-
mental modifications (and sometimes pharmacologic alternatives) rather than a further
increase in narcotics, which may just prolong the delirium.66
Careful attention to patients’ environment is part of the process of treating
delirium.67 Repeated reorientation of patients, use of eye glasses or hearing aids
when indicated, and minimization of excessive noise can be helpful. Keeping a child’s
favorite stuffed animal or blanket from home can normalize the ICU bed. Clustering
1126 Patel et al
care can dramatically reduce the frequency of stimulation.9,25,39 Creating an environ-

ment less disruptive to sleep is important – ensuring lights off at night and on during
the day helps to promote normal circadian rhythms.68 Early mobilization has been
an effective intervention in adult ICUs, not only in reducing poor functional outcomes,
but also in decreasing delirium rates.69 Progressive increase in activity levels can be
safely achieved, even in extremely young and MV children.70
Most pediatric delirium will improve with management of underlying medical
illness, minimizing iatrogenic triggers, and optimizing the PICU environment. How-
ever, if the delirium persists and the child has agitated behaviors that are distressful
or interfering with the medical care plan, pharmacologic therapies are available. Most
experts recommend use of the atypical antipsychotics because of their procognitive
effects and favorable side effect profile.3,71,72 This therapy is an off-label use, as this
drug class is not approved for treatment of pediatric delirium. Nonetheless, a ran-
domized controlled trial of quetiapine (an atypical antipsychotic) as treatment of adult
delirium indicated a benefit; pediatric case series have suggested efficacy in chil-
dren.49,73–76 A retrospective safety study in 50 delirious children treated with quetia-
pine showed no serious adverse events.77 Important when starting any form of
antipsychotic is to monitor for QT prolongation, dysrhythmias, and extrapyramidal
side effects.72,78
Prevention
Delirium can be conceptualized as a hospital-acquired complication that results in
both short- and long-term adverse effects in survivors of pediatric critical illness. As
such, prevention of delirium is an important goal.3,6
Anecdotally, the culture within critical care units, both adult and pediatric, seems to
be changing. In years past, most critically ill children were sedated during their time in
the ICU. They were often physically restrained, kept on strict bed rest, and exposed to
noise and lights 24 hours a day. Although parents were allowed at the bedside, they
were discouraged from physically interacting with their child. Cognitive stimulation
was kept to a minimum. This practice was likely the result of the desire to spare chil-
dren from a traumatic hospitalization and/or to allow them to rest. When children
became agitated, they were labeled as difficult to sedate and sedating medications
(usually benzodiazepines) were increased further.53,54
However, recent research on post-ICU outcomes (including myopathy and cogni-
tive impairment) shows that neither the mind nor the body benefits from prolonged
periods of inactivity.3,79–81 In particular, use of deep sedation (specifically benzodiaz-
epines) in children leads to increased delirium and decreased sleep and may be asso-
ciated with delusional memories and posttraumatic stress disorder.82–85
The SCCM has endorsed an alternative approach in adult ICUs, termed analgo-
sedation, that is now being adopted in PICUs as well (Fig. 3). For most patients, seda-
tion is not necessary as first-line therapy. Rather, with an analgesic-first approach, the
goal is to optimize pain control and minimize sedation. With less sedation on board,
patients are less likely to develop iatrogenic delirium. They are better able to commu-
nicate pain, which in turn leads to better pain control. They are also more available to
participate in early mobilization. Family members and child life specialists provide age-
appropriate cognitive stimulation during the day, and the medical care team attempts
to optimize the PICU environment for nighttime sleep.3,83,86,87
With heightened awareness as to the frequency and seriousness of pediatric
delirium, implementation of an analgo-sedation approach, incorporation of early mobi-
lization, and involvement of family members in daily care, we may be able to prevent
delirium in at-risk children.
Fig. 3. Analgo-sedation. An analgesic-first approach avoids sedatives unless necessary. This

approach decreases frequency of delirium.
SUMMARY
Delirium is a frequent complication of pediatric critical illness. Universal screening is

feasible and necessary for early detection. This screening allows for targeted interven-
tion and identification of children at risk for short-term morbidity and mortality. Further
research is necessary to determine the long-term cognitive and psychological effects
of pediatric delirium, and interventional studies are needed to establish best practices
for treatment and prevention of delirium in critically ill children.
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Delirium in Pediatric

DELIRIUM IN PEDIATRIC CRITICAL ILLNESS

Pediatr Clin N Am 64 (2017) 1117–1132

Predisposing Risk Factors Precipitating Risk Factors

The CAPD is an observational screen that provides a longitudinal picture of a pedi-

Fig. 2. Delirium treatment algorithm. With a systematic approach to targeting underlying

care can dramatically reduce the frequency of stimulation.9,25,39 Creating an environ-

Fig. 3. Analgo-sedation. An analgesic-first approach avoids sedatives unless necessary. This

Delirium is a frequent complication of pediatric critical illness. Universal screening is

8. Silver G, Traube C, Kearney J, et al. Detecting pediatric delirium: development of

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